Brief Title
Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma
Official Title
A Phase 2 Clinical Trial of Rituximab, Cyclophosphamide, Bortezomib (VELCADE), and Dexamethasone (R-CYBOR-D) in Relapsed Low Grade and Mantle Cell Lymphoma
Brief Summary
This phase II trial is studying how well giving rituximab and cyclophosphamide together with
bortezomib and dexamethasone (R-CyBor-D) works in treating patients with relapsed or
refractory low-grade follicular lymphoma, Waldenstrom macroglobulinemia, or mantle cell
lymphoma. Monoclonal antibodies, such as rituximab, can block cancer growth in different
ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and
help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of
cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in
chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the
growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving
rituximab and bortezomib together with combination chemotherapy may kill more cancer cells.
Detailed Description
PRIMARY OBJECTIVES:
I. To assess tumor response to R-CyBor-D in patients with relapsed follicular (Gr 1 or 2),
mantle cell, marginal zone lymphomas, small lymphocytic lymphoma (SLL)/chronic lymphocytic
leukemia (CLL) and lymphoplasmacytic (Waldenstrom's macroglobulinemia) lymphoma.
SECONDARY OBJECTIVES:
I. To evaluate overall survival, progression-free survival, duration of response, and time to
treatment failure of patients receiving R-CyBor-D.
II. To describe the adverse event profile (using National Cancer Institute [NCI] Common
Terminology Criteria for Adverse Events [CTCAE] v 3.0) of R-CyBor-D.
III. To evaluate quality of life for patient reported neurotoxicity using the Gynecologic
Oncology Group's Functional Assessment of Cancer Therapy (FACT/GOG) neurotoxicity
questionnaire, version 4.0.
OUTLINE:
Patients receive rituximab intravenously (IV) on day 1and cyclophosphamide orally (PO),
bortezomib IV, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days
for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for up to 3
years.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Proportion of Responses (Complete Response or Partial Response)
Secondary Outcome
Overall Survival
Condition
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
Intervention
Bortezomib
Study Arms / Comparison Groups
Treatment (R-CYBOR-D)
Description: Patients receive rituximab IV on day 1and cyclophosphamide PO, bortezomib IV, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
21
Start Date
August 2008
Completion Date
April 6, 2018
Primary Completion Date
November 2013
Eligibility Criteria
Inclusion Criteria:
- Histological confirmation of relapsed or refractory follicular Grades 1 or 2 lymphoma,
mantle cell lymphoma (MCL), small lymphocytic lymphoma/chronic lymphocytic leukemia
(SLL/CLL), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid
tissue (MALT) type, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell
lymphoma, or lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia/WM) by biopsy
≤ 6 months prior to registration
- NOTE: MCL diagnosis should be confirmed by cyclin D1 staining or fluorescence in
situ hybridization (FISH) (t(11;14))
- Measurable disease by computed tomography (CT), positron emission tomography (PET)/CT
or magnetic resonance imaging (MRI) scans with lymph nodes ≥2.0 cm in at least one
dimension or tumor cells in the blood ≥ 5 x10^9/L
- NOTE: Lymphoplasmacytic lymphoma (WM) patients without lymphadenopathy must have
1.) >10% lymphocytes, lymphoplasmacytic cells or plasma cells on a bone marrow
aspirate/biopsy, and 2.) quantitative IgM ≥ 400mg/dL
- Expected survival > 3 months
- ECOG Performance Status (PS) 0, 1 or 2
- Absolute Neutrophil Count ≥ 1200
- Platelet ≥ 75000
- Hemoglobin ≥ 8.0 g/dL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Alkaline phosphatase ≤ 3 x ULN
- Aspartate aminotransferase (AST) ≤ 3 x ULN
- Creatinine ≤ 1.5 x ULN
- Female subject is either postmenopausal for at least 1 year before the screening
visit, is surgically sterilized or if they are of childbearing potential, agree to
practice 2 effective methods of contraception from the time of signing the informed
consent form through 30 days after the last dose of VELCADE (bortezomib), or agree to
completely abstain from heterosexual intercourse
- Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree
to 1 of the following: practice effective barrier contraception during the entire
study treatment period and through a minimum of 30 days after the last dose of study
drug, or completely abstain from heterosexual intercourse
- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care
- Willingness to return to Mayo Clinic institution for follow-up
- Negative serum pregnancy test done <7 days prior to registration, for women of
childbearing potential only
- Willingness to complete questionnaires by themselves or with assistance
Exclusion Criteria:
- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown:
- Pregnant women -- confirmation that the subject is not pregnant must be
established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy
test result obtained during screening. Pregnancy testing is not required for
post-menopausal or surgically sterilized women;
- Nursing women;
- Men or women of childbearing potential who are unwilling to employ adequate
contraception
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and adverse event of the
prescribed regimen
- Patients known to be human immunodeficiency virus (HIV) positive
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm
- Diagnosed or treated for another malignancy ≤ 3 years prior to registration, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy or low-risk prostate cancer after curative therapy
- NOTE: If there is a history of prior malignancy, they must not be receiving other
specific treatment (other than hormonal therapy) for their cancer
- Patient has received other investigational drugs ≤ 14 days prior to registration
- Patient has hypersensitivity to bortezomib, boron or mannitol
- Myocardial infarction ≤ 6 months prior to registration or has New York Heart
Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities
- NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at Screening
has to be documented by the investigator as not medically relevant
- Previous cancer therapy, hormonal therapy and surgery < 4 weeks prior to registration
- Patient has ≥ Grade 2 peripheral neuropathy
- Radiation therapy within 3 weeks before randomization
- Enrollment of subjects who require concurrent radiotherapy (which must be
localized in its field size) should be deferred until the radiotherapy is
completed and 3 weeks have elapsed since the last date of therapy
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Craig Reeder, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00711828
Organization ID
MC0883
Secondary IDs
NCI-2011-02991
Responsible Party
Sponsor
Study Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Craig Reeder, Principal Investigator, Mayo Clinic
Verification Date
April 2019